Avibactam reverts the ceftazidime MIC90 of European Gram-negative bacterial clinical isolates to the epidemiological cut-off value

Abstract

Objectives:

Ceftazidime-avibactam consists of the beta-lactam ceftazidime and the novel non-beta-lactam beta-lactamase inhibitor avibactam. The effect of avibactam on the ceftazidime MIC frequency distribution of Gram-negative European clinical isolates was observed and compared to European Committee for Antimicrobial Susceptibility Testing (EUCAST) MIC frequency distributions and epidemiological cut-off values (ECOFFs) listed for ceftazidime.

Methods:

Ceftazidime and ceftazidime-avibactam MICs were determined using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods for Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Enterobacter spp., and Proteus mirabilis isolates collected from medical centres in Europe during 2009.

Results:

The MIC₉₀ values for ceftazidime and ceftazidime-avibactam against P. aeruginosa isolates from a 2009 European surveillance programme were >32 and 8 mg/l, respectively. That is, the presence of avibactam reverted the ceftazidime MIC₉₀ for P. aeruginosa to the ECOFF. Similarly, the MIC₉₀ values for ceftazidime against E. coli, Klebsiella spp., Serratia spp., and P. mirabilis were also reduced to the ECOFF by the presence of avibactam. Avibactam reduced the ceftazidime MIC₉₀ value against collected Enterobacter spp. to 1 mg/l (>32-fold reduction). No ECOFF has been defined for Enterobacter spp. however, it is 1 mg/l for Enterobacter aerogenes and Enterobacter cloacae.

Conclusions:

The presence of avibactam reverted the ceftazidime MIC₉₀ for Gram-negative bacteria to the ECOFF.

Keywords:

• Ceftazidime-avibactam
• ECOFF
• Gram-negative bacteria

Acknowledgements

Funding: This study at JMI Laboratories was supported by an Educational/Research grant from AstraZeneca, and JMI Laboratories received compensation fees for services in relation to preparing the manuscript, which was funded by AstraZeneca.

This work was previously reported in abstract form: Flamm et al. Avibactam reverts the ceftazidime MIC₉₀ of a recent set of European clinical isolates of Gram-negative bacteria back to the epidemiological cut-off value. Abstr. E-87, Presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2012 Sep; San Francisco, USA.

Transparency declarations: JMI Laboratories, Inc.(RKF, RNJ, and HSS) has received research and educational grants in 2010–2012 from – Achaogen, Aires, American Proficiency Institute (API), Anacor, Astellas, AstraZeneca, bioMerieux, Cempra, Cerexa, Contrafect, Cubist, Dipexium, Enanta, Furiex, GlaxoSmithKline, Johnson & Johnson, LegoChem Biosciences Inc., Meiji Seika Kaisha, Nabriva, Novartis, Pfizer, PPD Therapeutics, Premier Research Group, Rempex, Rib-X Pharmaceuticals, Seachaid, Shionogi, The Medicines Co., Theravance, ThermoFisher, and some other corporations. Some JMI employees are advisors/consultants for Astellas, Cubist, Pfizer, Cempra, Cerexa-Forest, and Theravance. GGS and WWN are employees of AstraZeneca Pharmaceuticals LP.